Data from Nature Communications - Curated by Marshall Pearce - Date added 08 December 2017

New findings may pave the way for novel HIV drugs

 

Tatyana Polenova and Juan Perilla, professors in the Department of Chemistry and Biochemistry at the University of Delaware, with a computer-generated model of HIV, the virus that causes AIDS.
Source: University of Delaware/ Evan Krape and Jeffrey Chase.

 

Human Immunodeficiency Virus (HIV) infects and destroys certain immune cells, leading to the gradual degradation of the immune system which unchecked, develops into acquired immunodeficiency syndrome (AIDS). AIDS has claimed the lives of more than 35 million people since its discovery in the 1980s.

A recent study led by researchers from the Universities of Delaware and Pittsburgh revealed a mechanism that disrupts the formation of HIV’s capsid ‒ the protein shell of a virus ‒ interfering with the virus’s ability to develop into an infectious agent.

The researchers studied the structure and dynamics of HIV in the early and later stages of its life cycle, measuring the movement of individual molecules within the virus and simulating this process. This technique allows for the visualisation of the viral maturation process where the non-infectious immature virion turns into an infectious virus particle.

The researchers discovered that a key peptide in HIV called Spacer Peptide 1 (SP1) is cut by viral proteases only when it is in a highly mobile structure, believed to resemble a thin strand attached to α-helical segments. Cleaving of SP1 triggers the formation of the capsid allowing the virus to become infectious.

The ability to stop or alter this process can prevent viral maturation, as shown by the anti-HIV inhibitor bevirimat. The targeting of this mechanism could prove to be a potent treatment and prevention therapy for HIV, creating a new generation of capsid inhibitors.

The team highlighted the importance of collaboration within the scientific community in order to make use of the wide range of specialist skills and equipment needed for this type of research, without which this finding would not have been possible.

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